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Jian-Jun Gou,1,* Na Liu,1,2,* Li-Hua Guo,2 Hao Xu,2 Tao Lv,2 Xiao Yu,2 Yun-Bo Chen,2 Xiao-Bing Guo,1 Yu-Ting Rao,1 Bei-Wen Zheng2 1Department of Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-Jun Gou; Bei-Wen Zheng Tel +86 371 6627 8237; +86 571 8723 6423Fax +86 371 6691 3569; +86 571 8723 6421Email jianjung@zzu.edu.cn; zhengbw@zju.edu.cnPurpose: To investigate the occurrence and genetic characteristics of the blaIMP-26-positive plasmid from a multidrug-resistant clinical isolate, Enterobacter hormaechei L51.Methods: Species identification was determined by MALDI-TOF MS and Sanger sequencing. Antimicrobial susceptibility testing was performed by the agar dilution and broth microdilution. Whole-genome sequencing was conducted using Illumina HiSeq 4000-PE150 and PacBio Sequel platforms, and the genome was annotated by the RAST annotation server. The ANI analysis of genomes was performed using OAT. Phylogenetic reconstruction and analyses were performed using the Harvest suite based on the core-genome SNPs of 61 publicly available E. hormaechei genomes.Results: The E. hormaechei L51 genome consists of a 5,018,729 bp circular chromosome and a 343,918 bp conjugative IncHI2/2A plasmid pEHZJ1 encoding blaIMP-26 which surrounding genetic context was intI1-blaIMP-26-ltrA-qacE∆1-sul1. A new sequence type (ST1103) was assigned for the isolate L51 which was resistant to cephalosporins, carbapenems, but sensitive to piperacillin-tazobactam, amikacin, tigecycline, trimethoprim-sulfamethoxazole and colistin. Phylogenetic analysis demonstrated that E. hormaechei L51 belonged to the same subspecies as the reference strain E. hormaechei SCEH020042, however 18,248 divergent SNP were identified. Resistance genes in pEHZJ1 including aac(3)-IIc, aac(6ʹ)-IIc, blaSHV-178, blaDHA-1, blaTEM-1, blaIMP-26, ereA2, catII, fosA5, qnrB4, tet(D), sul1 and dfrA19.Conclusion: In our study, we identified a conjugative IncHI2/2A plasmid carrying blaIMP-26 and blaSHV-178 in E. hormaechei ST1103, a novel multidrug-resistant strain isolated from China, and describe the underlying resistance mechanisms of the strain and detailed genetic context of mega plasmid pEHZJ1.Keywords: Enterobacter hormaechei, multidrug-resistant, blaIMP-26, IncHI2/2A, genomics

Manni Wang,* Xuelei Ma,* Linghong Guo, Fan Xia State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China *These authors contributed equally to this work Background: The aim of the present review is to systematically evaluate the efficacy and safety of pembrolizumab by analyzing survival outcomes and at the same time, to present evidence for future clinical applications of anti-programmed cell death protein 1 (anti-PD-1) antibodies by analyzing the efficacy and safety of pembrolizumab.Methods: A comprehensive literature search of PubMed, Medline, and Embase was performed for all relevant clinical trials. In this study, adverse events of any grades and grades ≥3 were summarized and calculated for event rates. For controlled trials, odd ratios (ORs) were calculated to determine the role of pembrolizumab in adverse events. The Kaplan–Meier survival curves were extracted for hazard ratio (HR) calculation and survival outcomes were measured by progression-free survival (PFS).Results: A total of 3,953 patients were included in safety analyses. The results indicated that the overall incidence of any treatment emergent adverse events was 74.3% (95% confidence interval [CI]: 0.671–0.805). The efficacy analysis involving 915 patients with advanced melanoma suggested that 10 mg/kg of pembrolizumab every 3 weeks could improve patients’ PFS (HR =0.73, 95% CI: 0.64–0.83).Conclusion: Pembrolizumab is a promising therapeutic option that could bring better survival outcomes but, at the same time, leads to higher frequency of some adverse events. Keywords: pembrolizumab, safety, efficacy, meta-analysis

Xiaoping Luo,1,2 Linghong Guo,1 Xi-Jian Dai,3 Qinglai Wang,2 Wenzhong Zhu,2 Xinjun Miao,2 Honghan Gong1 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nangchang, Jiangxi, People’s Republic of China; 2Department of Radiology, Wenzhou Chinese Medicine Hospital, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China Objective: To explore the abnormal intrinsic functional hubs in alcohol dependence using voxelwise degree centrality analysis approach, and their relationships with clinical features.Materials and methods: Twenty-four male alcohol dependence subjects free of medicine (mean age, 50.21±9.62 years) and 24 age- and education-matched male healthy controls (mean age, 50.29±8.92 years) were recruited. The alcohol use disorders identification test and the severity of alcohol dependence questionnaire (SADQ) were administered to assess the severity of alcohol craving. Voxelwise degree centrality approach was used to assess the abnormal intrinsic functional hubs features in alcohol dependence. Simple linear regression analysis was performed to investigate the relationships between the clinical features and abnormal intrinsic functional hubs.Results: Compared with healthy controls, alcohol dependence subjects exhibited significantly different degree centrality values in widespread left lateralization brain areas, including higher degree centrality values in the left precentral gyrus (BA 6), right hippocampus (BA 35, 36), and left orbitofrontal cortex (BA 11) and lower degree centrality values in the left cerebellum posterior lobe, bilateral secondary visual network (BA 18), and left precuneus (BA 7, 19). SADQ revealed a negative linear correlation with the degree centrality value in the left precentral gyrus (R2=0.296, P=0.006).Conclusion: The specific abnormal intrinsic functional hubs appear to be disrupted by alcohol intoxication, which implicates at least three principal neural systems: including cerebellar, executive control, and visual cortex, which may further affect the normal motor behavior such as an explicit type of impaired driving behavior. These findings expand our understanding of the functional characteristics of alcohol dependence and may provide a new insight into the understanding of the dysfunction and pathophysiology of alcohol dependence. Keywords: alcohol addiction, substance dependence, degree centrality, functional magnetic resonance imaging, functional connectivity driving behavior

Recently, light has been shed on possible interrelations between the two most important pathological hallmarks of Alzheimer's disease (AD): the amyloid cascade and axonal degeneration. In this study, we investigated associations between sβAPPβ, a product of the cleavage of the amyloid-β protein precursor (AβPP) by β-secretase, amyloid-β 1-42 (Aβ42), soluble SORL1 (also called LR11 or SORLA), a receptor that is involved in AβPP processing, and the marker of axonal degeneration tau in the cerebrospinal fluid (CSF) of 76 patients with mild cognitive impairment (MCI), 61 patients with AD, and 17 patients with frontotemporal dementia, which neuropathologically is not related to the amyloid pathology. In the AD group, significant associations between sAβPPβ, tau (p < 0.001), and soluble SORL1 (p < 0.001) were detected according to linear regression models. In patients with MCI, sAβPPβ correlated significantly with tau (p < 0.001) and soluble SORL1 (p = 0.003). In the FTD group, only SORL1 (p = 0.011) was associated with sAβPPβ and not tau. Aβ42 was found to be significantly related to tau levels in CSF in the MCI group (p < 0.001) and they tended to be associated in the AD group (p = 0.05). Our results provide further evidence for a link between the two facets of AD pathology, which is likely to be mediated by the binding of Aβ oligomers to specifically targeted neurons, resulting in stimulating tau hyperphosphorylation and neurodegeneration. [ABSTRACT FROM AUTHOR]

This study aimed to explore the isomer-specific, sex-specific, and joint associations of PFAS and red blood cell indices. We used data of 1,238 adults from the Isomers of C8 Health Project in China. Associations of PFAS isomers and red blood cell indices were explored using multiple linear regression models, Bayesian Kernel Machine Regression models and subgroup analysis across sex. We found that serum concentration of linear (n-) and branched (Br-) isomers of perfluorooctane sulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) were significantly associated with red blood cell indices in single-pollutant models, with stronger associations observed for n-PFHxS than Br-PFHxS, in women than in men. For instance, the estimated percentage change in hemoglobin concentration for n-PFHxS (3.65%; 95% CI: 2.95%, 4.34%) was larger than that for Br-PFHxS (0.96%; 95% CI: 0.52%, 1.40%). The estimated percentage change in red blood cell count for n-PFHxS in women (2.55%; 95% CI: 1.81%, 3.28%) was significantly higher than that in men (0.12%; 95% CI: -1.04%, 1.29%) ( P inter < 0.001). Similarly, sex-specific positive association of PFAS mixture and outcomes was observed. Therefore, the structure, susceptive population, and joint effect of PFAS isomers should be taken into consideration when evaluating the health risk of chemicals.

Ingestion of perfluoroalkyl acids (PFAAs) via contaminated food contact materials (FCMs) is an important human exposure source. This study adopts a toxicity equivalent approach to evaluate the collective health risk of multiple PFAAs in FCMs. A comprehensive extraction and analysis of 21 PFAAs in FCMs was performed. Among the analyzed substances, 15 PFAAs were detected. Migration experiment using three food simulants revealed the migration range of seven PFAAs from FCMs into the simulant to be 0.47-46.7 ng/cm 2 . The hazard quotient results suggest minimal health risk, except for 9% of packaged samples where perfluorooctanoic acid (PFOA) poses a higher risk. Utilizing PFOA toxic equivalent concentrations, comprehensive risk calculations showed ∼77% of samples potentially posing elevated health risks due to PFAA exposure. This emphasizes the substantial contribution of PFAAs beyond PFOA and underscores the importance of considering them in related assessments. The aggregated risk assessment reflects actual exposure circumstances more accurately., (© 2024 Institute of Food Technologists.)

In recent years, the prevalence and danger of organophosphorus flame retardants (OPFRs) have drawn attention from all around the world. This study examined twenty-five OPFRs observed in water and sediment samples from the Qiantang River in eastern China, as well as their occurrence, spatial distribution, possible origins, and ecological hazards. All the 25 OPFRs were detected in water and sediment samples. The levels of Σ 25 OPFRs in water and sediment were 35.5-192 ng/L and 8.84-48.5 ng/g dw, respectively. Chlorinated OPFRs were the main contributions in water, whereas alkyl-OPFRs were the most common congeners found in sediment. Spatial analysis revealed that sample locations in neighboring cities had somewhat higher water concentrations of OPFRs. Slowing down the river current and making the reservoir the main sink of OPFRs, the dam can prevent OPFRs from moving via the Qiantang River. Positive matrix factorization indicated that plasticizer in polyvinyl chloride, polyester resins, and polyurethane foam made the greatest contributions in water, whereas polyurethane foam and textile were the predominant source in sediment. Analysis of sediment-water exchange of OPFRs showed that twelve OPFRs in sediments can re-enter into the water body. The risk quotients showed the ecological risk was low to medium, but trixylyl phosphate exposures posed high ecological risk to aquatic organisms., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Megalurothrips usitatus (Bagnall) (Thysanoptera: Thripidae) and Frankliniella intonsa (Trybom) (Thysanoptera: Thripidae) have been detrimental to cowpea production in many countries. Laboratory experiments were conducted to determine the prey stage preference and functional response of 2 predatory mites species, Neoseiulus barkeri (Hughes) (Acari: Phytoseiidae), and Neoseiulus californicus (McGregor) (Acari: Phytoseiidae), towards 2 thrips species (TS), M. usitatus, and F. intonsa, at varying densities and life stages on cowpea. Results shown that Neoseiulus species had a preference for different life stages of prey. Neoseiulus barkeri consumed more M. usitatus nymphs, while N. californicus consumed more F. intonsa (second-instar nymphs). The functional response of the 2 Neoseiulus spp. to nymphs of 2 TS was Type II on cowpea. The higher attack rate coefficient (a') and shorter handling time (Th) values were found on N. barkeri against M. usitatus, and a similar trend was found for those in N. californicus against F. intonsa. Field-caged trials were conducted to evaluate the effectiveness of Neoseiulus spp. in controlling 2 TS. The results have shown that Neoseiulus spp. was effective in controlling the 2 TS, with varying control efficacies at high or low release rates. The study provided valuable information on using Neoseiulus spp. as biological control agents against M. usitatus and F. intonsa in cowpea crops., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

As alternatives of perfluorooctanoic acid (PFOA), hexafluoropropylene oxide dimeric acid (HFPO-DA) and trimeric acid (HFPO-TA) have been detected increasingly in environmental media and even humans. They have been shown to exhibit reproductive toxicity to model species, but their effects on human remain unclear due to the knowledge gap in their mode of action. Herein, (anti-)androgenic effects of the two HFPOs and PFOA were investigated and underlying toxicological mechanism was explored by combining zebrafish test, cell assay and molecular docking simulation. Exposure of juvenile zebrafish to the chemicals during sex differentiation promoted feminization, with HFPO-TA acting at an environmental concentration of 1 μg/L. The chemicals inhibited proliferation of human prostate cells and transcriptional activity of human and zebrafish androgen receptors (AR), with HFPO-TA displaying the strongest potency. Molecular docking revealed that the chemicals bind to AR in a conformation similar to a known AR antagonist. Combined in vivo, in vitro and in silico results demonstrated that the chemicals disrupted sex differentiation likely by antagonizing AR-mediated pathways, and provided more evidence that HFPO-TA is not a safe alternative to PFOA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To understand the epidemiological characteristics of fatal drowning in children in Zhejiang Province in 2022, analyze factors such as the swimming ability of children, the caregiver behavior at drowning site, types of first aid personnel and methods of first aid of unintentional fatal drowning and provide evidence for targeted intervention. Methods: Using the "Survey Form of Fatal Drowning Case in Children" designed by National Center for Chronic and Non-communicable Disease Control and Prevention of the China CDC, we collected case information of children aged 0-17 years who died due to drowning in Zhejiang in 2022 from medical history/death investigation records, telephone interviews, and home visits. Results: A total of 341 fatal drowning cases in children occurred in Zhejiang in 2022 and 330 cases were investigated (96.77%). The male to female of the cases was 2.33∶1, most cases were aged 15-17 years and 0-4 years, and 54.24% of fatal drowning cases occurred in children from other provinces. In the drowning cases, 83.33% were unintentional ones, and the proportion of intentional fatal drowning cases in children increased with age. Fatal drowning cases mainly occurred in open natural water bodies and public water storage facilities. More fatal drowning cases occurred in open natural water bodies in older children, while more fatal drowning cases occurred in public water storage facilities in younger children. In 275 children who died due to unintentional drowning, 73.09% could not swim, and only 1.09% were fully supervised by adults within an arm's length. First aid personnel, mainly medical staffs, bystanders and adult caregivers, were present for 47.63% fatal drowning cases. The proportion of the cases who had cardiopulmonary resuscitation as the first aid within 5 minutes was 2.18%. Conclusions: Drowning poses a serious threat to children's lives and there are differences in reasons and locations of fatal drowning in children in different age groups in Zhejiang Province in 2022. It is necessary to conduct to interventions to improve children's swimming skills, strengthen effective adult care and conduct health education about field first aid of drowning to reduce the incidence of drowning and related deaths in children.

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1β, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The potential association between colorectal cancer (CRC) and environmental pollutants is worrisome. Previous studies have found that some perfluoroalkyl acids, including perfluorooctane sulfonate (PFOS), induced colorectal tumors in experimental animals and promoted the migration of and invasion by CRC cells in vitro, but the underlying mechanism is unclear. Here, we investigated the effects of PFOS on the proliferation and migration of CRC cells and the potential mechanisms involving activating the PI3K/Akt-NF-κB signal pathway and epithelial-mesenchymal transition (EMT). It was found that PFOS promoted the growth and migration of HCT116 cells at non-cytotoxic concentrations and increased the mRNA expression of the migration-related angiogenic cytokines vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). In a mechanistic investigation, the up-stream signal pathway PI3K/Akt-NF-κB was activated by PFOS, and the process was suppressed by LY294002 (PI3K/Akt inhibitor) and BAY11-7082 (NF-κB inhibitor) respectively, leading to less proliferation of HCT116 cells. Furthermore, matrix metalloproteinases (MMP) and EMT-related markers were up-regulated after PFOS exposure, and were also suppressed respectively by LY294002 and BAY11-7082. Moreover, the up-regulation of EMT markers was suppressed by a MMP inhibitor GM6001. Taken together, our results indicated that PFOS promotes colorectal cancer cell migration and proliferation by activating the PI3K/Akt-NF-κB signal pathway and epithelial-mesenchymal transition. This could be a potential toxicological mechanism of PFOS-induced malignant development of colorectal cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: This study aimed to explore the differences between tall-cell subtype of papillary thyroid carcinoma (TCPTC) and classical papillary thyroid carcinoma (cPTC) using multimodal ultrasound, and identify independent risk factors for TCPTC to compensate the deficiency of preoperative cytological and molecular diagnosis on PTC subtypes., Methods: Forty-six TCPTC patients and 92 cPTC patients were included. Each patient received grey-scale ultrasound, colour Dopplor flow imaging (CDFI) and shear-wave elastography (SWE) preoperatively. Clinicopathologic information, grey-scale ultrasound features, CDFI features and SWE features of 98 lesions were compared using univariate analysis to find out predictors of TCPTC, based on which, a predictive model was built to differentiate TCPTC from cPTC and validated with 40 patients., Results: Univariate and multivariate analyses identified that extra-thyroidal extension (odds ratio [OR], 15.12; 95% CI, 2.26-115.44), aspect ratio (≥0.91) (OR, 29.34; 95% CI, 1.29-26.23), and maximum diameter ≥14.6 mm (OR, 20.79; 95% CI, 3.87-111.47) were the independent risk factors for TCPTC. Logistic regression equation: P = 1/1+ExpΣ[-5.099 + 3.004 × (if size ≥14.6 mm) + 2.957 × (if aspect ratio ≥ 0.91) + 2.819 × (if extra-thyroidal extension). The prediction model had a good discrimination performance for TCPTC: the area under the receiver-operator-characteristic curve, sensitivity, and specificity were 0.928, 0.848, and 0.954 in cohort 1, and the corresponding values in cohort 2 were 0.943, 0.923, and 0.926, respectively., Conclusion: Ultrasound has the potential for differential diagnosis of TCPTC from cPTC. A prediction model based on ultrasound characteristics (extra-thyroidal extension, aspect ratio ≥0.91, and maximum diameter ≥14.6 mm) was useful in predicting TCPTC., Advances in Knowledge: Multimodal ultrasound prediction of TCPTC was a supplement to preoperative cytological diagnosis and molecular diagnosis of PTC subtypes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Many antibiotic disinfection byproducts have been detected but their toxicity has not been evaluated adequately. In this report, the chlorination reaction kinetics of five common sulfamides (SAs), reaction intermediates and their toxicity were investigated. Chlorination of sulfapyridine (SPD), sulfamethazine (SMT), sulfathiazole (STZ), and sulfisoxazole (SIZ) followed the second-order kinetics, and were degraded completely within 10 min. A large number of reaction intermediates were deteced by LC-MS, among which a total of 16 intermediates were detected for the first time. Toxicity of the five SAs chlorination solutions was evaluated separately by examining their effects on the growth rate of S. salivarius K12, a commensal bacterium in the human digestive system. After 30 min chlorination, solutions of SMT, STZ and sulfadiazine (SDZ) each exhibited severe toxicity by inhibiting the bacteria growth completely, whereas the inhibition was only 50 % and 20  % by SIZ and SPD respectively. Based on the comparison between toxicity test results and mass spectra, three SA chlorination intermediates, m/z 187.2 (C 10 H 10 N 4 ), m/z 287.2 (C 9 H 7 N 3 O 4 S 2 ) and m/z 215 (C 7 H 10 N 4 O 2 S/C 12 H 14 N 4 ) were proposed to be the primary toxicants in the chlorination products. Our study demonstrated the power of combined approach of chemical analysis and toxicity testing in identifying toxic disinfection byproducts, and highlighted the ne ed for more research on the toxicity evaluation and risk assessment of antibiotic disinfection byproducts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Graft-versus-host disease (GVHD), an immunological disorder that arises from donor T cell activation through recognition of host alloantigens, is the major limitation in the application of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Traditional immunosuppressive agents can relieve GVHD, but they induce serious side effects. It is highly required to explore alternative therapeutic strategy. Human amniotic epithelial stem cells (hAESCs) were recently considered as an ideal source for cell therapy with special immune regulatory property. In this study, we evaluated the therapeutic role of hAESCs in the treatment of GVHD, based on our previous developed cGMP-grade hAESCs product. Humanized mouse model of acute GVHD (aGVHD) was established by injection of huPBMCs via the tail vein. For prevention or treatment of aGVHD, hAESCs were injected to the mice on day -1 or on day 7 post-PBMC infusion, respectively. We showed that hAESCs infusion significantly alleviated the disease phenotype, increased the survival rate of aGVHD mice, and ameliorated pathological injuries in aGVHD target organs. We demonstrated that hAESCs directly induced CD4 + T cell polarization, in which Th1 and Th17 subsets were downregulated, and Treg subset was elevated. Correspondingly, the levels of a series of pro-inflammatory cytokines were reduced while the levels of the anti-inflammatory cytokines were upregulated in the presence of hAESCs. We found that hAESCs regulated CD4 + subset polarization in a paracrine mode, in which TGFβ and PGE2 were selectively secreted to mediate Treg elevation and Th1/Th17 inhibition, respectively. In addition, transplanted hAESCs preserved the graft-versus-leukemia (GVL) effect by inhibiting leukemia cell growth. More intriguingly, hAESCs infusion in HSCT patients displayed potential anti-GVHD effect with no safety concerns and confirmed the immunoregulatory mechanisms in the preclinical study. We conclude that hAESCs infusion is a promising therapeutic strategy for post-HSCT GVHD without compromising the GVL effect. The clinical trial was registered at www.clinicaltrials.gov as #NCT03764228., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Purpose: To explore the feasibility of a 5G-based telerobotic ultrasound (US) system for providing qualified abdominal US services on a rural island., Methods: This prospective study involved two medical centers (the tele-radiologist site's hospital and the patient site's hospital) separated by 72 km. Patients underwent 5G-based telerobotic US by tele-radiologists and conventional US by on-site radiologists from September 2020 to March 2021. The clinical feasibility and diagnostic performance of the 5G-based telerobotic abdominal US examination were assessed based on safety, duration, image quality, diagnostic findings, and questionnaires., Results: A total of 401 patients (217 women and 184 men; mean age, 54.96 ± 15.43 years) were enrolled. A total of 90.1% of patients indicated no discomfort with the telerobotic US examination. For the examination duration, telerobotic US took longer than conventional US (12.54 ± 3.20 min vs. 7.23 ± 2.10 min, p = 0.001). For image quality scores, the results of the two methods were similar (4.54 ± 0.63 vs. 4.57 ± 0.61, p = 0.112). No significant differences were found between the two methods in measurements for the aorta, portal vein, gallbladder, kidney (longitudinal diameter), prostate, and uterus; however, telerobotic US underestimated the transverse diameter of the kidney (p < 0.05). A total of 504 positive results, including 31 different diseases, were detected. Among them, 455 cases were identified by the two methods; 17 cases were identified by telerobotic US only; and 32 cases were identified by conventional US only. There was good consistency in the diagnosis of 29 types of disease between the two methods (κ = 0.773-1.000). Furthermore, more than 90% of patients accepted the telerobotic US examination and agreed to pay additional fees in future., Conclusion: The 5G-based telerobotic US system can expand access to abdominal US services for patients in rural areas, thereby reducing health care disparities., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There are few studies on the health effects of long-term exposure to neighborhood greenness in a longitudinal setting, especially in Asian countries with high population densities., Objectives: This study investigates the association between long-term exposure to neighborhood greenness and hypertension among adults in Taiwan., Methods: We selected 125,537 participants ( ≥ 18  years of age) without hypertension from Taiwan who had joined the standard medical examination program between 2001 and 2016. Neighborhood greenness was estimated using the normalized difference vegetation index (NDVI), derived from satellite images at a resolution of 250   m 2 . The 2-y average NDVI value within a 500 -m circular buffer around participants' residences was calculated. A time-varying Cox regression model was used to investigate the association between neighborhood greenness and incident hypertension. Mediation analyses were performed to examine whether the association was explained by air pollution, leisure-time physical exercise, or body mass index (BMI)., Results: Compared with living in areas within the first quartile of neighborhood greenness, living in areas within the second, third, and fourth quartiles of neighborhood greenness was found to be associated with a lower risk of hypertension, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.95 (95% CI: 0.91, 1.00), 0.95 (95% CI: 0.90, 0.99), and 0.93 (95% CI: 0.88, 0.97), respectively. Each 0.1-unit increase in the NDVI was associated with a 24% lower risk of developing hypertension ( HR = 0.76; 95% CI: 0.66, 0.87), with this associations being stronger among males and those with higher education levels. This association was slightly mediated by BMI but not by air pollution or leisure-time physical exercise., Discussion: Our findings suggest the protective effects of neighborhood greenness on hypertension development, especially in males and well-educated individuals. Our results reinforced the importance of neighborhood greenness for supporting health. https://doi.org/10.1289/EHP13071.

Objective: To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults. Methods: A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test. Results: A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI : 2.23-3.88) points ( P <0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI : 4.03-5.37) points ( P <0.001). Ba Duan Jin showed significant improvement ( P <0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions: This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Information on the spatio-temporal patterns of the burden of ischemic heart disease (IHD) caused by ambient ambient fine particulate matter (PM 2.5 ) in the global level is needed to prioritize the control of ambient air pollution and prevent the burden of IHD. The Global Burden of Disease Study (GBD) 2019 provides data on IHD attributable to ambient PM 2.5 . The IHD burden and mortality attributable to ambient PM 2.5 were analyzed by year, age, gender, socio-demographic index (SDI) level, geographical region and country. Estimated annual percentage change (EAPC) was calculated to estimate the temporal trends of age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR) from 1990 to 2019. Globally, the ASMR and ASDR for ambient PM 2.5 -related IHD tended to level off generally, with EAPC of -0.03 (95% CI: -0.06, 0.12) and 0.3 (95% CI: 0.22, 0.37), respectively. In the past 30 years, there were obvious differences in the trend of burden change among different regions. A highest increased burden was estimated in low-middle SDI region (EAPC of ASMR: 3.73 [95% CI: 3.56, 3.9], EAPC of ASDR: 3.83 [95% CI: 3.64, 4.02]). In contrast, the burden in high SDI region (EAPC of ASMR: -4.48 [95% CI: -4.6, -4.35], EAPC of ASDR: -3.98 [95% CI: -4.12, -3.85]) has declined most significantly. Moreover, this burden was higher among men and older populations. EAPCs of the ASMR (R = -0.776, p < 0.001) and ASDR (R = -0.781, p < 0.001) of this burden had significant negative correlations with the countries' SDI level. In summary, although trends in the global burden of IHD attributable to ambient PM 2.5 are stabilizing, but this burden has shifted from high SDI countries to middle and low SDI countries, especially among men and elderly populations. To reduce this burden, the air pollution management prevention need to be further strengthened, especially among males, older populations, and middle and low SDI countries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Clinical appearance and high-frequency ultrasound (HFUS) are indispensable for diagnosing skin diseases by providing internal and external information. However, their complex combination brings challenges for primary care physicians and dermatologists. Thus, we developed a deep multimodal fusion network (DMFN) model combining analysis of clinical close-up and HFUS images for binary and multiclass classification in skin diseases., Methods: Between Jan 10, 2017, and Dec 31, 2020, the DMFN model was trained and validated using 1269 close-ups and 11,852 HFUS images from 1351 skin lesions. The monomodal convolutional neural network (CNN) model was trained and validated with the same close-up images for comparison. Subsequently, we did a prospective and multicenter study in China. Both CNN models were tested prospectively on 422 cases from 4 hospitals and compared with the results from human raters (general practitioners, general dermatologists, and dermatologists specialized in HFUS). The performance of binary classification (benign vs. malignant) and multiclass classification (the specific diagnoses of 17 types of skin diseases) measured by the area under the receiver operating characteristic curve (AUC) were evaluated. This study is registered with www.chictr.org.cn (ChiCTR2300074765)., Findings: The performance of the DMFN model (AUC, 0.876) was superior to that of the monomodal CNN model (AUC, 0.697) in the binary classification ( P  = 0.0063), which was also better than that of the general practitioner (AUC, 0.651, P  = 0.0025) and general dermatologists (AUC, 0.838; P  = 0.0038). By integrating close-up and HFUS images, the DMFN model attained an almost identical performance in comparison to dermatologists (AUC, 0.876 vs. AUC, 0.891; P  = 0.0080). For the multiclass classification, the DMFN model (AUC, 0.707) exhibited superior prediction performance compared with general dermatologists (AUC, 0.514; P  = 0.0043) and dermatologists specialized in HFUS (AUC, 0.640; P  = 0.0083), respectively. Compared to dermatologists specialized in HFUS, the DMFN model showed better or comparable performance in diagnosing 9 of the 17 skin diseases., Interpretation: The DMFN model combining analysis of clinical close-up and HFUS images exhibited satisfactory performance in the binary and multiclass classification compared with the dermatologists. It may be a valuable tool for general dermatologists and primary care providers., Funding: This work was supported in part by the National Natural Science Foundation of China and the Clinical research project of Shanghai Skin Disease Hospital., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Author(s).)

Objectives: To investigate whether the integration of high-frequency ultrasound (HFUS) to routine clinical examinations could improve diagnostic performance and management decision for pigmented skin tumors., Methods: Three general practitioners trained previously and a dermatologist independently assessed pigmented skin tumors and rendered management decision based on clinical examinations alone or clinical examinations integrating HFUS., Results: After integrating HFUS, the diagnostic area under the curve (AUC) (0.658-0.693 versus 0.848, all P < .05) and specificity (46.6-58.6% versus 89.7%, all P < .05) for pigmented skin malignancies were improved for general practitioners, meanwhile unnecessary biopsy rate reduced (42.9-53.6% versus 10.7%, P < .001). To the dermatologist, the diagnostic AUC (0.822 versus 0.949, P < .001), sensitivity (81.7% versus 96.7%, P = .012) and specificity (0.828 versus 0.931, P = .031) improved significantly, meanwhile both missed biopsy rate (14.5% versus 4.8%, P = .031) and unnecessary biopsy rate (19.6% versus 7.1%, P = .016) decreased. Additionally, the diagnostic performance of the general practitioner with integrating HFUS could be comparable with the dermatologist based on clinical examinations alone (all P > .05)., Conclusions: As a complementary tool of clinical examinations, HFUS could help physicians differentiate pigmented skin malignancies and manage decision., (© 2023 American Institute of Ultrasound in Medicine.)

The thrips Megalurothrips usitatus Bagnall and Frankliniella intonsa Trybom (Thysanoptera: Thripidae) are important pests in cowpea-growing areas of south China. Parthenogenesis is an important reproductive form of thysanopterans, and plays an important role in maintaining population growth. To understand the developmental and reproductive characteristics of these 2 thrips species during parthenogenesis, we compared the age-stage life tables of M. usitatus and F. intonsa on cowpea pods under natural regimes during the summer and winter. The results showed that the total preadult period and total preoviposition period of M. usitatus were significantly longer than those of F. intonsa in both seasons. Moreover, longevity of adult M. usitatus (29.53 days) was shorter compared with adult F. intonsa (34.00 days) in summer, whereas higher fecundity (220.8 eggs/female) and more oviposition days (37.83 days) were observed in M. usitatus compared with F. intonsa in winter (fecundity = 179.83 eggs/female, oviposition days = 33.03 days). The net and gross reproductive rates of M. usitatus were significantly greater than those of F. intonsa during winter. In addition, the intrinsic and finite rates of increase of M. usitatus were significantly lower than those of F. intonsa, and the mean generation time of M. usitatus was significantly longer than that of F. intonsa both in summer and winter. These results indicated that parthenogenesis has species specificity among thrips, which in turn affects population development, especially under changing environments., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America.)

Purpose of Review: The increasing prevalence of cardiometabolic risk factors (CRFs) contributes to the rise in cardiovascular disease. Previous research has established a connection between air pollution and both the development and severity of CRFs. Given the ongoing impact of air pollution on human health, this review aims to summarize the latest research findings and provide an overview of the relationship between different types of air pollutants and CRFs., Recent Findings: CRFs include health conditions like diabetes, obesity, hypertension etc. Air pollution poses significant health risks and encompasses a wide range of pollutant types, air pollutants, such as particulate matter (PM), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), and ozone (O 2 ). More and more population epidemiological studies have shown a positive correlation between air pollution and CRFs. Although various pollutants have diverse effects on specific cellular molecular pathways, their main influence is on oxidative stress, inflammation response, and impairment of endothelial function. More and more studies have proved that air pollution can promote the occurrence and development of cardiovascular and metabolic risk factors, and the research on the relationship between air pollution and CRFs has grown intensively. An increasing number of studies are using new biological monitoring indicators to assess the occurrence and development of CRFs resulting from exposure to air pollution. Abnormalities in some important biomarkers in the population (such as homocysteine, uric acid, and C-reactive protein) caused by air pollution deserve more attention. Further research is warranted to more fully understand the link between air pollution and novel CRF biomarkers and to investigate potential prevention and interventions that leverage the mechanistic link between air pollution and CRFs., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Hepatocelluar carcinoma presenting as a biliary duct tumor thrombus is a relatively rare entity, with poor prognosis. The primary clinical manifestation of this disease is obstructive jaundice, which can often be misdiagnosed. A 59-year-old female patient was admitted with sudden onset of abdominal pain. Laboratory tests suggested obstructive jaundice, and enhanced magnetic resonance imaging of the upper abdomen did not show obvious biliary dilatation. Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography suggested an occupying lesion in the upper bile duct. SpyGlass and biopsy finally confirmed hepatocellular carcinoma with right hepatic duct tumor thrombus hemorrhage. The SpyGlass Direct Visualization System, as an advanced biliary cholangioscopy device, showed the advantages of single-person operation as well as easy access to and visualization of the lesion.

Perfluorooctanoic acid (PFOA) alternatives such as hexafluoropropylene oxide homologs (HFPOs) cause concern due to increased occurrence in the environment as well as potential bioaccumulation and toxicity. HFPOs have been demonstrated to activate the estrogen receptor (ER) pathway. The ER pathway is homologous and connected to the estrogen-related receptor (ERR) pathway, but HFPOs effects on the ERR pathway have not been studied. Hence, we assessed the potential estrogenic effects of HFPOs via ERRγ pathway. In vitro assays revealed that HFPO dimeric, trimeric, and tetrameric acids (HFPO-DA, -TA, and -TeA, respectively), acted as ERRγ agonists, activating the transcription of both human and zebrafish ERRγ at low concentrations, but inhibiting zebrafish ERRγ at high concentrations. We also found that HFPO-TA promoted the human endometrial cancer cells (Ishikawa cells) proliferation via ERRγ/EGF, Cyclin D1 pathway. The HFPO-TA-induced proliferation of Ishikawa cells was inhibited by co-exposure with a specific antagonist of ERRγ, GSK5182. In vivo exposure of female zebrafish to HFPO-TA disturbed sex hormone levels, interfered with the gene expression involved in estrogen synthesis and follicle regulation, and caused histopathological lesions in the ovaries, which were similar to those induced by a known ERRγ agonist GSK4716. Taken together, this study revealed a new mechanism concerning the estrogenic effect of HFPOs via activation of the ERRγ pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Metalaxyl (MET) and myclobutanil (MYC) are two widely used chiral fungicides that may pose health risks to non-occupationally exposed populations. Here, the two fungicides were enantiomer-specific quantified in the dietary food and urine of residents in an Eastern China city, to determine the exposure and excretion of these contaminants in different populations. Results indicate that residues of MET and MYC varied with different food items at 0.42-0.86 ng/g fresh weight (FW) and 0.18-0.33 ng/g FW, respectively. In urine samples, the residual levels after creatinine adjusting (CR) ranged from 10.2 to 1715.4 ng/g CR for MET and were below the detection limit up to 320.7 ng/g CR for MYC. Significant age- and gender-related differences were separately found in urinary MET and MYC of different populations. Monte-Carlo simulations suggested that children had higher daily dietary intake (DDI) but lower urinary excretion (DUE) rates than youths, and thus may suffer higher body burdens. The residues of antifungally ineffective enantiomers (S-MET and R-MYC) were slightly higher than their antipodes in foods. Moreover, the enantiomer-selective urinary excretion resulted in higher retention of S-MET and R-MYC in the human body. Our results suggest that both dietary intake and urinary excretion should be enantiomer-specifically considered when assessing the exposure risk and body burden of chiral fungicides in the non-occupationally exposed population. Furthermore, substitutive application of enantiomer-enriched fungicide formulations can not only benefit the antifungal efficacy but also be safer for human health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Environmental occurrence and human exposure of emerging organophosphate esters (eOPEs) have increased significantly in recent years. Resorcinol bis(diphenyl) phosphate (RDP) is one of the major eOPEs detected in indoor dust, but the knowledge on its toxicities and health risks is rather limited. In this study, we investigated the in vitro estrogenic effects and underlying mechanism of RDP in comparison with a legacy OPE triphenyl phosphate (TPHP). Our results showed that RDP promoted MCF-7 cell proliferation with the lowest effect concentration of 2.5 μM, and the maximum enhancement of 1.6 folds is greater than that of TPHP (1.3 folds). The effect was inhibited completely by an estrogen receptor (ER) antagonist, suggesting that ER activation was responsible for the enhancement. In luciferase reporter gene assays both RDP and TPHP activated ER transcriptional activity at 2.5 μM, but RDP activity was higher than TPHP. Competitive fluorescence binding assays showed that RDP bound to ER with an IC 10 of 0.26 μM, which is 20 folds lower than TPHP (5.6 μM). Molecular docking simulation revealed that both RDP and TPHP interacted with ER at the binding pocket of estradiol, although the hydrogen bonds were different. Taken together, RDP exerted stronger estrogenic effects than TPHP through ER-mediated pathways and may pose more health risks., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Maternal exposure to environment toxicants is an important risk factor for neurobehavioral health in their offspring. In our study, we investigated the impact of maternal exposure to chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs, commercial name: F-53B) on behavioral changes and the potential mechanism in the offspring larvae of zebrafish. Adult zebrafish exposed to Cl-PFESAs (0, 0.2, 2, 20 and 200 μg/L) for 21 days were subsequently mated their embryos were cultured for 5 days. Higher concentrations of Cl-PFESAs in zebrafish embryos were observed, along with, reduced swimming speed and distance travelled in the offspring larvae. Molecular docking analysis revealed that Cl-PFESAs can form hydrogen bonds with brain-derived neurotropic factor (BDNF), protein kinase C, alpha, (PKCα), Ca 2+ -ATPase and Na, K - ATPase. Molecular and biochemical studies evidenced Cl-PFESAs induce dopaminergic dysfunction, eye developmental defects and disrupted Ca 2+ homeostasis. Together, our results showed that maternal exposure to Cl-PFESAs lead to behavioral alteration in offspring mediated by disruption in Ca 2+ homeostasis, dopaminergic dysfunction and eye developmental defects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Systemic neonicotinoid insecticides (NEOs) applied by seed-treatment or root application have emerged as a prevalent strategy for early-season insect pest management. This research investigated the effectiveness of imidacloprid and thiamethoxam, administered through root irrigation, in managing thrips in cowpea [Vigna unguiculata (Linn.) Walp.], and the residual properties of both insecticides in cowpea and soil. The results show that thrips density depends on the application rate of insecticides. At the maximum application rate (1,500 µg/ml, active ingredient), imidacloprid and thiamethoxam controlled thrips densities below the economic injury level (EIL, the EIL of thrips on cowpea was 7/flower) for 20 days and 25 days with the density of 6.90 and 6.93/flower at the end of the periods, respectively. Imidacloprid and thiamethoxam residues decreased gradually over time and decreased sharply after 15 days after treatment (DAT), the 2 insecticides were not detected (<0.001 mg/kg) at 45 DAT. According to our findings, the application of imidacloprid and thiamethoxam via root irrigation proved residual control lasting up to 20-25 days for controlling thrips damage at experimental rates, with a strong association to their residual presence in cowpea (0.6223 < R2 < 0.9545). Considering the persistence of the imidacloprid and thiamethoxam, the maximum tested application rate (1,500 µg/ml) was recommended. As the residues of imidacloprid and thiamethoxam were undetectable in cowpea pods at all tested rates, it may be suggested that the use of each insecticide is safe for consumers and effective against thrips, and could be considered for integrated thrips management in the cowpea ecosystem., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America.)

Environmental pollutants exposure might disrupt cardiac function, but evidence about the associations of per- and polyfluoroalkyl substances (PFASs) exposure and cardiac conduction system remains sparse. To explore the associations between serum PFASs exposure and electrocardiogram (ECG) parameters changes in adults, we recruited 1229 participants (mean age: 55.1 years) from communities of Guangzhou, China. 13 serum PFASs with detection rate > 85% were analyzed finally. We selected 6 ECG parameters [heart rate (HR), PR interval, QRS duration, Bazett heart rate-corrected QT interval (QTc), QRS electric axis and RV5 + SV1 voltage] as outcomes. Generalized linear models (GLMs) and Bayesian kernel machine regression (BKMR) model were conducted to explore the associations of individual and joint PFASs exposure and ECG parameters changes, respectively. We detected significant associations of PFASs exposure with decreased HR, QRS duration, but with increased PR interval. For example, at the 95th percentile of 6:2 Cl-PFESA, HR and QRS duration were - 6.98 [95% confidence interval (CI): - 9.07, - 4.90] and - 6.54(95% CI: -9.05, -4.03) lower, but PR interval was 7.35 (95% CI: 3.52, 11.17) longer than those at the 25th percentile. Similarly, significant joint associations were observed in HR, PR interval and QRS duration when analyzed by BKMR model., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Rural general practitioners (GPs) have insufficient diagnostic information to deal with complex clinical scenarios due to the inequality in medical imaging resources in rural and remote communities. The objective of this study is to explore the value of a tele-mentored handheld ultrasound (tele-HHUS) system, allowing GPs to provide ultrasound (US) services in rural and remote communities., Methods: Overall, 708 patients underwent tele-HHUS examination between March and October 2021 and March and April 2022 across thirteen primary hospitals and two tertiary-care general hospitals. All US examinations were guided and supervised remotely in real time by US experts more than 300 km away using the tele-HHUS system. The following details were recorded: location of tele-HHUS scanning, primary complaints, clinical diagnosis, and US findings. The recommendations (referral or follow-up) based on clinical experience alone were compared with those based on clinical experience with tele-HHUS information., Results: Tele-HHUS examinations were performed both in hospital settings (90.6%, 642/708) and out of hospital settings (9.4%, 66/708). Leaving aside routine physical examinations, flank pain (14.2%, 91/642) was the most common complaint in inpatients, while chest distress (12.1%, 8/66) and flank discomfort (12.1%, 8/66) were the most common complaints in out-of-hospital settings. Additionally, the referral rate increased from 5.9% to 8.3% (kappa = 0.202; p = 0.000)., Conclusions: The tele-HHUS system can help rural GPs perform HHUS successfully in remote and rural communities. This novel mobile telemedicine model is valuable in resource-limited areas.

Background: It is unknown whether high-frequency ultrasound (HFUS) can evaluate invisible subcutaneous lesions. We aimed to investigate the diagnostic value of HFUS in invisible subcutaneous lesions., Method: Patients with invisible subcutaneous lesions were prospectively recruited from two centres. Before undergoing biopsy or surgery, each lesion was independently evaluated by two clinicians. One provides a clinical diagnosis by only clinical examination and the other provides an integrated diagnosis by combining clinical examination and HFUS information. Diagnoses were classified as correct, wrong, and indeterminate. A total of 391 lesions from 355 patients were enrolled, including 225 epidermoid cysts, 77 lipomas, 25 pilomatrixomas, 21 haemangiomas, 19 dermatofibromas, 11 dermatofibrosarcoma protuberans (DFSP), 7 neurofibromas, and 6 leiomyomas. Using pathological results as the gold standard, diagnostic performance was compared., Results: The number of correct diagnoses increased from 185 (47.3%) by clinical examination alone to 316 (80.8%) after the addition of HFUS (P < 0.05). Meanwhile, the indeterminate diagnosis rate decreased from 143 (36.6%) to 10 (2.6%). Using HFUS, the accuracy improved significantly for epidermoid cysts (59.6% vs. 86.7%), lipomas (50.6% vs. 94.8%), pilomatrixomas (0% vs. 48.0%), haemangiomas (23.8% vs. 57.1%), and DFSPs (0% vs. 81.8%) (all p < 0.05). However, HFUS did not significantly improve the diagnostic accuracy of dermatofibromas (15.8% vs. 21.1%, p > 0.999), neurofibromas (42.9% vs. 71.4%, p = 0.625), or leiomyomas (16.7% vs. 100%, p = 0.063)., Conclusion: Combining HFUS and clinical examination can generally improve the diagnostic accuracy and decrease the indeterminacy of invisible subcutaneous lesions, especially epidermoid cysts, lipomas, pilomatrixomas, haemangiomas, and DFSPs. However, for some rare lesions, HFUS cannot provide useful information., (© 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Objectives: This study was aimed to evaluate the diagnostic performance of ultrasound (US) in differentiating trichilemmal cysts (TCs) from epidermoid cysts (ECs)., Methods: Based on clinical and ultrasound features, a prediction model was established and validated. 164 cysts in the pilot cohort and another 69 in the validation cohort diagnosed with TCs or ECs histopathologically were evaluated. The same radiologist performed all ultrasound examinations., Results: For clinic features, TCs tended to occur in females compared with ECs (66.7 vs 28.5%; P < .001). In addition, TCs were prone to occur in the hairy area compared with ECs (77.8 vs 13.1%; P < .001). For ultrasound features, the internal hyperechogenicity and cystic change were more likely to appear in TCs in comparison with ECs (92.6 vs 25.5%; P < .001; 70.4 vs 23.4%; P < .001, respectively). Upon the features mentioned above, a prediction model was established with the areas under the receiver operating characteristic curves of 0.936 and 0.864 in the pilot and validation cohorts, respectively., Conclusions: US is promising for differentiating TCs from ECs and is valuable for their clinical management., (© 2023 American Institute of Ultrasound in Medicine.)

Anthropogenic heat has been reported to have significant health impacts, but research on its association with childhood adiposity is still lacking. In this study, we matched the 2008-2012 average anthropogenic heat flux, as simulated by a grid estimation model using inventory methods, with questionnaire and measurement data of 49,938 children randomly recruited from seven cities in Northeast China in 2012. After adjusting for social demographic and behavioral factors, we used generalized linear mixed-effect models to assess the association between anthropogenic heat flux and adiposity among children. We also examined the effect modification of various social demographic and behavioral confounders. We found that each 10 W/m 2 increase in total anthropogenic heat flux and that from the industry source was associated with an increase of 5.82% (95% CI = 0.84%-11.05%) and 6.62% (95% CI = 0.87%-12.70%) in the odds of childhood adiposity. Similarly, the excess rate of adiposity among children were 5.26% (95% CI = -1.33%-12.29%) and 8.51% (95% CI = 2.24%-15.17%) per 1 W/m 2 increase in the anthropogenic heat flux from transportation and buildings, and was 7.94% (95% CI = 2.28%-13.91%) per 0.001 W/m 2 increase in the anthropogenic heat flux from human metabolism. We also found generally greater effect estimates among female children and children who were exposed to passive smoking during pregnancy, born by caesarean section, non-breastfed/mixed-fed, or lived within 20 m adjacent to the main road. The potential deleterious effect of anthropogenic heat exposure on adiposity among children may make it a new but major threat to be targeted by future mitigation strategies., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Antifouling biocides may cause adverse effects on non-target species. This study aims to determine the distribution, sources, and ecological risks of antifouling biocides in the surface waters of the Qiantang River and its estuary in eastern China. The concentrations of total antifouling biocides were ranged from 12.9 to 215 ng/L for all water samples. Atrazine, diuron and tributyltin were the major compounds in the water bodies of the study area. The acute and chronic toxicity criteria for tributyltin, diuron and atrazine were derived for freshwater and saltwater, respectively, based on the species sensitivity distribution approach. The freshwater and saltwater criteria were slightly different, and the toxicity to aquatic organisms could be summarized as tributyltin > diuron > atrazine. The graded ecological risk rating showed that the long-term risk of TBT was significant in coastal waters. The pollution of TBT in the Qiantang River deserves further attention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Two thrips, Megalurothrips usitatus (Bagnall) and Frankliniella intonsa (Trybom) are major pests of cowpea in South China. To realistically compare the growth, development and reproductive characteristics of these two thrips species, we compared their age-stage, two-sex life tables on cowpea pods under summer and winter natural environmental regimes. The results showed that the total preadult period of M. usitatus was 8.09 days, which was significantly longer than that of F. intonsa (7.06 days), while the adult female longevity of M. usitatus (21.14 days) was significantly shorter than that of F. intonsa (25.77 days). Significant differences were showed in male adult longevity (10.68 days for F. intonsa and 16.95 days for M. usitatus ) and the female ratio of offspring (0.67 for F. intonsa and 0.51 for M. usitatus ), and the total preadult period of M. usitatus (16.20 days) was significantly longer than that of F. intonsa (13.66 days) in the winter regime. The net reproductive rate (summer: R 0 = 85.62, winter: R 0 = 105.22), intrinsic rate of increase (summer: r = 0.3020 day -1 , winter: r = 0.2115 day -1 ), finite rate of increase (summer: λ = 1.3526 day -1 , winter: λ = 1.2356 day -1 ) and gross reproduction rate (summer: GRR = 139.34, winter: GRR = 159.88) of F. intonsa were higher than those of M. usitatus (summer: R 0 = 82.91, r = 0.2741, λ = 1.3155, GRR = 135.71; winter: R 0 = 80.62, r = 0.1672, λ = 1.1820, GRR = 131.26), and the mean generation times (summer: T = 14.73 days, winter: T = 22.01 days) of F. intonsa were significantly shorter than those of M. usitatus (summer: T = 16.11 days, winter: T = 26.25 days). These results may contribute to a better understanding of the bioecology of different thrips species, especially the interspecific competition between two economically important cowpea thrips with the same ecological niche in a changing environment.

Environmental and human monitoring studies have witnessed increasing occurrence of emerging per-/poly-fluoroalkyl substances (ePFASs) worldwide. Three classes of ePFASs, namely chlorinated polyfluoroalkylether sulfonic acids, hexafluoropropylene oxide homologues and short-chain perfluoroalkyl acids attracted the most attention. It is, therefore, the goal of this review to systematically and critically analyse the toxicity and toxicological mechanisms of these ePFASs based on the papers published between 2017 and 2022. The review summarized the main findings from both in vivo and in vitro studies, covering the hepatotoxicity of ePFASs and their interference with the endocrine system, including reproductive, developmental and thyroid toxicity. It also summarized the changes in gene expression in the hypothalamic-pituitary-thyroid axis and hypothalamic-pituitary-gonad axis of the model organisms after ePFASs exposure. The changes in gene expression in vitro and in vivo provide a clearer understanding of the toxicological mechanisms of ePFASs interference on hormonal levels (i.e., estradiol, testosterone, and thyroid hormones), developmental disturbance (e.g., swim bladder dysfunction) and lipid metabolism disruption (e.g., lipid droplet accumulation and hepatomegaly). In the end, future research directions on the toxicological mechanisms of ePFASs are suggested., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Worldwide, gastric cancer (GC) is a common lethal solid malignancy with a poor prognosis. Cuproptosis is a novel type of cell death mediated by protein lipoylation and may be related to GC prognosis., Aim: To offer new insights to predict GC prognosis and provide multiple therapeutic targets related to cuproptosis-related genes (CRGs) for future therapy., Methods: We collected data from several public data portals, systematically estimated the expression level and prognostic values of CRGs in GC samples, and investigated related mechanisms using public databases and bioinformatics., Results: Our results revealed that FDX1 , LIAS , and MTF1 were differentially expressed in GC samples and exhibited important prognostic significance in The Cancer Genome Atlas (TCGA) cohort. We constructed a nomogram model for overall survival and disease-specific survival prediction and validated it via calibration plots. Mecha-nistically, immune cell infiltration and DNA methylation prominently affected the survival time of GC patients. Moreover, protein-protein interaction network, KEGG pathway and gene ontology enrichment analyses demonstrated that FDX1 , LIAS , MTF1 and related proteins play key roles in the tricarboxylic acid cycle and cuproptosis. Gene Expression Omnibus database validation showed that the expression levels of FDX1 , LIAS , and MTF1 were consistent with those in the TCGA cohort. Top 10 perturbagens has been filtered by Connectivity Map., Conclusion: In conclusion, FDX1 , LIAS , and MTF1 could serve as potential prognostic biomarkers for GC patients and provide novel targets for immunotarget therapy., Competing Interests: Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The accumulation of antibiotics in the environment has ecological impacts that have received less attention than the human health risks of antibiotics, although the effects could be far-reaching. This review discusses the effects of antibiotics on the health of fish and zooplankton, manifesting in direct or dysbiosis-mediated physiological impairment. Acute effects of antibiotics in these organism groups are usually induced at high concentrations (LC 50 at ∼100-1000 mg/L) that are not commonly present in aquatic environments. However, when exposed to sub-lethal, environmentally relevant levels of antibiotics (ng/L-μg/L) disruption of physiological homeostasis, development, and fecundity can occur. Antibiotics at similar or lower concentrations can induce dysbiosis of gut microbiota which can affect the health of fish and invertebrates. We show that the data about molecular-level effects of antibiotics at low exposure concentrations are limited, hindering environmental risk assessment and species sensitivity analysis. Fish and crustaceans (Daphnia sp.) were the two groups of aquatic organisms used most often for antibiotic toxicity testing, including microbiota analysis. While low levels of antibiotics impact the composition and function of gut microbiota in aquatic organisms, the correlation and causality of these changes to host physiology are not straightforward. In some cases, negative or lack of correlation have occurred, and, unexpectedly, gut microbial diversity has been unaffected or increased upon exposure to environmental levels of antibiotics. Efforts to incorporate functional analyses of gut microbiota are beginning to provide valuable mechanistic information, but more data is needed for ecological risk assessment of antibiotics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: We assessed muscle mass and function using ultrasound (US) and shear wave elastography (SWE) for sarcopenia in elderly patients with type 2 diabetes., Methods: There were 84 patients with type 2 diabetes enrolled in this study; of these, 30 had sarcopenia and 54 did not. We measured appendicular skeletal muscle mass index (ASMI), handgrip strength, calf circumference, 6-m walking speed, and 5-time chair stand test. All patients were in the supine position with their knees in straight and bent poses in turn. The US-derived thickness (T straight , T bent ), cross-sectional area (CSA straight , CSA bent ), and SWE (SWE straight , SWE bent ) of the rectus femoris muscle (RFM) were measured and the differences (ΔT, ΔCSA, ΔSWE) were calculated. We assessed the correlations of clinical indicators with US and SWE features. We then compared the clinical indicators and US and SWE features between patients with and without sarcopenia to determine independent predictors. Diagnostic models were established based on these independent predictors., Results: The ASMI was correlated with T bent (r = 0.57, p < 0.001) and CSA bent (r = 0.50, p < 0.001). Handgrip strength was correlated with T bent (r = 0.53, p < 0.001) and CSA bent (r = 0.51, p < 0.001). Between patients with and without sarcopenia, the indicators of age, ΔCSA, and ΔSWE were statically different (all p ≤ 0.001). Based on these results, a diagnostic model for sarcopenia was established with 83.3% sensitivity, 83.3% specificity, and 83.3% accuracy., Conclusions: In elderly people with type 2 diabetes, sarcopenia patients had smaller muscle CSA and less stiffness than non-sarcopenia patients. US and SWE might be useful to screen them., Key Points: • Sarcopenia is common in elderly people with type 2 diabetes. • Ultrasound and shear wave elastography might be useful methods for quantitatively assessing muscle mass and strength. • Ultrasound and shear wave elastography might be useful methods for screening sarcopenia in elderly patients with type 2 diabetes., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Objective: To identify patients in the subclinical psoriatic arthritis (Sub-PsA) phase by ultrasound (US) and provide a solution to screen them., Methods: A total of 490 participants with moderate-to-severe psoriasis were evaluated. Among them, 384 participants without arthritis symptoms were enrolled into the silent psoriasis group and 106 participants with arthritis symptoms, called prodromal/active PsA phase, were enrolled into the clinical PsA group. Another 80 non-psoriasis participants were enrolled into the control group. Each participant received clinical assessments and US examinations of 60 joints, 38 tendons, and 40 entheses. We compared the incidences of synovio-enthesitis, synovitis, tenosynovitis, erosion, and dactylitis detected on US among the three groups. Subsequently, on the basis of significant US findings, we distinguished Sub-PsA from psoriasis alone (PsO) in the silent psoriasis group and analyzed the clinical characteristics, mainly including basic clinical characteristics, body surface area (BSA), and Psoriasis Area and Severity Index (PASI) score., Results: Only synovio-enthesitis significantly differed between the control group and the silent psoriasis group (1.3% vs. 16.1%, p < 0.001). The knee was the most commonly involved site of synovio-enthesitis (79.0%). Taking synovio-enthesitis as the standard, 16.1% of silent psoriasis participants and 12.7% of all psoriasis participants were in the Sub-PsA phase. Furthermore, there were no differences in BSA and PASI among the three phases of PsO, Sub-PsA, and prodromal/active PsA., Conclusions: Since the psoriasis patients in Sub-PsA phase was as high as 12.7% in all patients with moderate-to-severe psoriasis, US-detected synovio-enthesitis was recommended routinely for screening them regardless of arthritis symptoms, especially in the lower limbs., Key Points: • Synovio-enthesitis on ultrasound was significantly associated with subclinical psoriatic arthritis, especially in the lower limbs. • Routine ultrasound evaluation could help screen psoriasis patients in the subclinical psoriatic arthritis phase, which was as high as 12.7% in all psoriasis patients., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Adverse outcome pathway (AOP) as a conceptual framework is a powerful tool in the field of toxicology to connect seemingly discrete events at different levels of biological organizations into an organized pathway from molecular interactions to whole organism toxicity. Based on numerous toxicological studies, eight AOPs for reproductive toxicity have been endorsed by the Organization for Economic Co-operation and Development (OECD) Task Force on Hazard Assessment. We have conducted a literature survey on the mechanistic studies on male reproductive toxicity of perfluoroalkyl acids (PFAAs), a class of global environmental contaminants with high persistence, bioaccumulation and toxicity. Using the AOP development strategy, five new AOPs for male reproductive toxicity were proposed here, namely (1) changes in membrane permeability leading to reduced sperm motility, (2) disruption of mitochondrial function leading to sperm apoptosis, (3) decreased gonadotropin-releasing hormone (GnRH) expression in hypothalamus leading to reduced testosterone production in male rats, (4) activation of the p38 signaling pathway leading to disruption of BTB in mice, (5) inhibition of p-FAK-Tyr407 activity leading to the destruction of BTB. The molecular initiating events in the proposed AOPs are different from those in the endorsed AOPs, which are either receptor activation or enzyme inhibition. Although some of the AOPs are still incomplete, they can serve as a building block upon which full AOPs can be developed and applied to not only PFAAs but also other chemical toxicants with male reproductive toxicity., Competing Interests: Declaration of competing interest The authors declare they have no actual or potential competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The increasing population of diabetes mellitus in adolescent girls and women of childbearing age contributes to a large number of pregnancies with maternal pregestational diabetes mellitus. Congenital heart diseases are a common adverse outcome in mothers with pregestational diabetes mellitus. However, there is little systematic information between maternal pregestational diabetes mellitus and congenital heart diseases in the offspring., Data Sources: Literature selection was performed in PubMed. One hundred and seven papers were cited in our review, including 36 clinical studies, 26 experimental studies, 31 reviews, eight meta-analysis articles, and six of other types., Results: Maternal pregestational diabetes mellitus poses a high risk of congenital heart diseases in the offspring and causes variety of phenotypes of congenital heart diseases. Factors such as persistent maternal hyperglycemia, oxidative stress, polymorphism of uncoupling protein 2, polymorphism of adiponectin gene, Notch 1 pathway, Nkx2.5 disorders, dysregulation of the hypoxia-inducible factor 1, and viral etiologies are associated with the occurrence of congenital heart diseases in the offspring of mothers with pregestational diabetes mellitus. Treatment options including blood sugar-reducing, anti-oxidative stress drug supplements and exercise can help to prevent maternal pregestational diabetes mellitus from inducing congenital heart diseases., Conclusions: Our review contributes to a better understanding of the association between maternal pregestational diabetes mellitus and congenital heart diseases in the offspring and to a profound thought of the mechanism, preventive and therapeutic measurements of congenital heart diseases caused by maternal pregestational diabetes mellitus., (© 2022. Children's Hospital, Zhejiang University School of Medicine.)

Systemic inflammation markers have been highlighted recently as related to cardiac and non-cardiac disorders. However, few studies have estimated pre-diagnostic associations between these markers and hypertension. In the National Health and Nutritional Examination Survey from 1999 to 2010, 22,290 adult participants were included for analysis. We assessed associations between four systemic inflammation markers based on blood cell counts: systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and hypertension prevalence in multivariate logistic regression analysis with odds ratio (OR) and 95% confidence interval (CI). To further explore their associations, subgroup and sensitivity analyses were performed. In continuous analyses, the ORs for hypertension prevalence per ln-transformed increment in SII and NLR were estimated at 1.115 and 1.087 (95% CI: 1.045-1.188; 1.008-1.173; respectively). Compared to those in the lowest tertiles, the hypertension risks for subjects in the highest SII and NLR tertiles were 1.20 and 1.11 times, respectively. Conversely, we found that PLR and LMR were negatively associated with hypertension prevalence in continuous analyses (1.060, 0.972-1.157; 0.926, 0.845-1.014; respectively), and the highest PLR and LMR tertiles (1.041, 0.959-1.129; 0.943, 0.866-1.028; respectively). Also, subgroup and sensitivity analyses indicated that SII had a greater correlation to hypertension. In conclusion, we find positive associations between SII and NLR and the prevalence of hypertension in this cross-sectional study. Our findings highlight that SII may be a superior systemic inflammation warning marker for hypertension., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Toxicity screening and risk assessment of an overwhelmingly large and ever-increasing number of chemicals are vitally essential for ecological safety and human health. Genotoxicity is particularly important because of its association with mutagenicity, carcinogenicity and cancer. Phosphorylated histone H2AX (γH2AX) is an early sensitive genotoxic biomarker. It is therefore highly desirable to develop analytical methods for the detection of trace γH2AX to enable screening and assessment of genotoxicity. Here, we developed a novel cathodic photoelectrochemical (PEC) immunoassay with dual signal amplification for the rapid and ultrasensitive detection of γH2AX in cell lysates. A sandwich immuno-reaction targeting γH2AX was first carried out on a 96-well plate, using a secondary antibody/gold nanoparticle/glucose oxidase conjugate as the labeled detection antibody. The conjugate increased the production of H 2 O 2 and thus provided the first mechanism of signal amplification. The immuno-reaction product containing H 2 O 2 was then detected on a photocathode prepared from Bi 2+x WO 6 rich in oxygen vacancies, with H 2 O 2 acting as electron acceptor. The oxygen vacancies acted as both adsorption and activation sites of H 2 O 2 and thus enhanced the photocurrent, which provided another mechanism of signal amplification. As a result, an ultrasensitive immunoassay for γH2AX determination was established with a limit of detection of 6.87 pg/mL (S/N = 3) and a wide linear range from 0.01 to 500 ng/mL. The practicability of this assay was verified by detecting γH2AX in cell lysates exposed to known genotoxic chemicals. Our work offers a promising tool for the screening of genotoxic chemicals and opening a new avenue toward environmental risk assessment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)